The path to a COVID-19 vaccine – Expert Briefing

The SMC led an online media briefing about the process toward developing a COVID-19 vaccine and what role New Zealand might play.

Dr Helen Petousis-Harris, University of Auckland
Chair of the WHO’s Global Advisory Committee on Vaccine Safety

Professor Peter McIntyre, University of Otago
Member of the WHO’s Strategic Advisory Group of Experts (SAGE) on Immunisation

The full briefing is available here.

A transcripted Q&A is below – further resources on COVID-19 vaccine development are available here.

What kind of precedent do we have for developing a vaccine very quickly, amidst an outbreak? I’m thinking in particular of recent experience with the Ebola outbreak.

Peter McIntyre

“The Ebola outbreak was in some ways the genesis of a lot of what’s happening now because it had become clear when the crisis of the outbreak emerged (of course we need to remember that with Ebola we were talking about a disease with 50 per cent or higher mortality), that it was a much scarier disease than COVID-19. What became apparent as the scale of that outbreak was unfolding was that although the work on an Ebola vaccine had been going on for 20 years it had only progressed to the stage of looking at it in animals, so of course there was no human data and by the time initial human trials had been established and there was comfort about actually initiating a trial in the field in Africa, the epidemic was waning, fortunately.

“But the number of cases were few and that led everyone to say we need to do better than this. We need to be in a position where we’re thinking about potential causes of outbreaks in the future and actually looking to develop candidate vaccines. So there was a big initiative led by Norway, but supported strongly by the UK, US, Bill Gates etc to develop a coalition. They created the Coalition for Epidemic Preparedness Innovations (CEPI). We are where we are with COVID right now because CEPI had been working with partners to identify vaccines against a range of possible pandemic causing viruses. Although obviously COVID-19 wasn’t specifically anticipated, the possibility of a coronavirus was. The same groups that had been working with an Ebola vaccine had also been working with a SARS vaccine. So we did learn a lot and we are in a much better position than we would have been had this been happening back in 2014 when the world was confronted with Ebola.”

There seems to be a lot of optimism that there will be a vaccine – maybe one, maybe more. Is that likely and do we have any precedent for effective coronavirus vaccines?

Peter McIntyre

“We do have some limited precedence in this in that work was done on SARS. Fortunately for us, SARS fizzled out because although it was very infectious by the time you got severe disease from SARS it really wasn’t infectious from asymptomatic people prior to getting ill and being in hospital. So SARS turned out to be a much easier task and we didn’t need to deploy those vaccines. But I think from the SARS experience we’ve got information about what to watch out for to ensure we don’t have a situation where you receive a vaccine and if you get exposed to the virus you actually get a worse response so we are forewarned about being really careful to avoid that situation. And I think we’ve got much better knowledge about the factors that might lead to that.

“We do have some strong candidates so the eight groups that have been supported by CEPI are all obviously well along the path and have done, in some cases, even early human trials but certainly in all cases have got a whole lot of the important background, the laboratory work, done. So although amongst the 90 or 100 other groups that are also seeking a development vaccine it may be that one of those turns out to be the Willy Wonka golden chocolate wrapper. But I guess what we’re thinking is likely that given the amount of work and the track record of the vaccine that is chosen by CEPI is the best candidate probably the most likely scenario is that one of those will emerge. And out of that group of eight you’ve got vaccines which are using things we’re familiar with like an inactivated virus or a protein subunit from the SARS virus or a virus-like particle which was the novel technology used for the HPV vaccine which has been incredibly successful globally. And then we’ve got some things which have been around as ideas for a long time like the idea of using Messenger RNA or DNA, which are the codes for the building blocks for proteins as vaccines and I guess also the possibility of a weakened form of the SARS virus which we do have some experience with, with both Influenza and Measles, but it’s certainly a new thought for a SARS. There’s a lot of different approaches in the mix and given the track record and given the quality of groups that are working on these I think we’re right to have a high degree of confidence that something will turn up but what we’re looking at is an incredibly compressed process to even get to this trial stage which normally would take ten years so as a result of CEPI we’re in a position to see these trials rolling out now. And then to get to a stage of a successful trial of a vaccine actually available to be used at your local GP surgery would normally be another 10 years again so I guess the notion that we can condense that into a period of 12-18 months is a really new thing and the really challenging thing.”

There is a compressed timeframe to get a vaccine out at speed, does that compromise safety?

Helen Petousis-Harris

“I don’t think it has to compromise safety because while you’re doing a whole lot of things that are speeding this process up it doesn’t necessarily mean that you are skipping out important steps. There are also approaches to address any of the additional risks that we might see when we’re looking at a vaccine that’s been through clinical trials of thousands and not tens of thousands of people. You just don’t throw it into a population, we do have approaches, ways and means, to ensure that the safety of something is monitored very closely for the early period that’s the vaccines used.”

Are there particular safety issues that are of concern?

Helen Petousis-Harris

“There has been a list compiled of what’s called our adverse events of special interest. The idea behind the list is thinking about the types of disease the manifestations of COVID-19 are causing, so those are the symptoms like lung disease. There’s also the potential theoretical events that could be caused by the nature of the vaccine. So we’ve got all these different types of vaccines that Peter was talking about and are there any inherent properties in these vaccines that might cause a problem. So really brainstorming everything you can think of that could potentially, hypothetically be a problem. Making a list of these things and then focusing on those. So looking for those things specifically.”

There’s been a lot of discussion about whether New Zealand should be involved in developing a vaccine. Do we have precedent around this?

Helen Petousis-Harris

“New Zealand learned a lot through the process of developing the Meningococcal B vaccine for a devastating epidemic. While the vaccine was not made in New Zealand it was based on a vaccine that has been used in Norway and there was a collaboration between the New Zealand Government, University of Auckland, Norwegian Institute of Public Health and industry. So it was the company that was able to make the vaccine basically using the Norwegian template.

“The vaccine was tested in New Zealand right from the beginning. All the way through clinical trials and then when it was implemented. Because we had an emergency situation, people were dying, so it was rolled out to the highest-risk people first and it was monitored almost in real-time. People turned up to the general practice or to hospital and their exposure to the vaccine could be ascertained almost in real-time and the safety profile of the vaccine could be followed very, very closely. That was really seen globally as a gold standard. So we’ve been through some of these processes in New Zealand before very, very successfully.”

Assuming that a COVID-19 vaccine becomes available, how would you see it being used?

Helen Petousis-Harris

“In these sort of situations, and you’ve also got possibly limited supply of vaccine, you tend to look at those groups that are first of all the highest-risk groups, but also those who are the front-line professionals, who are both more likely to be exposed but also have a higher rate of severe consequences. So it’s very likely that maybe you’d see it targeted in older people, people with underlying conditions, and health professionals is my guess.”

Peter McIntyre

“One of the challenges I suppose with thinking about targeting is clearly targeting front-line health workers would be a predominantly younger, healthy population and would have fewer issues. But targeting the group that is at highest risk of bad outcomes from COVID, which are people over 70, people with significant existing diseases, those are the very people who tend to have the least robust, least protective response to the vaccines that we’re currently using.

“So in fact, the only example of a vaccine that’s come along so far which is really effective in the older, frailer population, is, in fact, the new Zoster or shingles vaccine – the trade name is Shingrix – which has been developed by GSK. It’s available in the US, it’s not available in New Zealand. That vaccine uses what’s called an adjuvant which is a kind of secondary component of the vaccine which isn’t itself producing antibodies but is able to stimulate stronger and more robust immune responses.

“If we were going to successfully initially use a COVID-19 vaccine in the high-risk older, frailer population we would really need to look at whether we had a vaccine candidate that was capable of producing strong antibody responses in that group.”

Where do you think New Zealand should be focusing its attention or funding?

Peter McIntyre

“I guess you have to be realistic about the size of this problem and the number of players who are involved with it. But as Helen said, New Zealand performed incredibly well in terms of both identifying and then testing and rolling out a vaccine for its meningococcal B epidemic in the 1990s. The capacity and particularly the capacity for monitoring in real-time for safety – which is something that may need to happen with this COVID vaccine, because once it’s there people won’t want to wait around too long, they’ll want to get on with it. And yet we won’t have experience in tens, hundreds or thousands or millions of people. That capacity that New Zealand’s demonstrated in MenzB, to be able to do that in real-time and roll out in the population – and obviously there’ll be a strong demand for this vaccine as well – it will be incredibly important.

If we have been successful in keeping the numbers of COVID-19 low in New Zealand, is there anything that might be useful in terms of a population for testing that hasn’t been exposed to a large degree?

Peter McIntyre

“I think as far as vaccine trials are concerned, obviously some of the earlier vaccine trials where we’re just looking at responses to the vaccine, I think New Zealand would be quite an attractive site for that because there’ll be pretty much an unexposed population who might put their hands up to be part of a study like that.

“For what’s called phase three trials, where you’re actually trying to identify whether the vaccine protects you against disease, then I guess New Zealand’s in the fortunate situation where it’s not going to be a site for that kind of trial and I suppose we should all be thankful about that.”

If – when – there is an effective vaccine what does it look like in terms of manufacturing? Is there capacity around the world to manufacture enough vaccine to meet the demand?

Peter McIntyre

“I guess it’s an unprecedented task, because we’re not just talking about the usual target groups of sufficient vaccine for all newborn babies or all pregnant women. The closest analogy is flu vaccine where countries like the US have aimed not just to get it to their over 65-year-olds, or their under-five-year-olds, but in the US to get it to everyone. If you think of the scale of that task if we wanted to produce a vaccine that’s potentially available for all age groups in all places.

“There are some really interesting initiatives in terms of groups like the Serum Institute in India – which is currently, in world terms, the largest vaccine manufacturer in the world – undertaking to actually produce one of the vaccines, the adenovirus one from the University of Oxford, under licence and to start doing that right now even though they haven’t seen the final trial results. Bill Gates is undertaking to fund a number of new vaccine manufacturing facilities. I think that’s the kind of capacity that’s going to be needed. And if there are existing facilities in New Zealand that for instance have manufacturing vaccines for animals that are in a position to rapidly scale up and contribute to that production capacity, including for our Pacific neighbours, then that would be a great initiative to see.”